Serotonergic antidepressants, emotional numbness and sexual dysfunction

[Neuroprotection]

Yes and no. It only has because most people with depression don't have depression. Like if you can say "I'm anxious about..." or "I'm depressed because..." then you don't have an anxiety disorder or depression, you're experiencing a normal emotional reaction to something. But a lot of people in those situations get prescribed anti-depressants (and I'm not saying they necessarily shouldn't) but they make up the majority of people diagnosed with those conditions and obviously they don't have any sort of imbalance.
For me, no type of thinking/talking therapy has ever made any difference at all, but medications have made a big difference.

EDIT: I actually watched a documentary on the harm of psych meds not that long ago and I think the real results on SSRI/SNRI's were that about 1/3rd of people benefitted from then, they were ineffective (or made negligible difference) in around 1/3rd of people and had a negative impact on about 1/3rd of people.
I wouldn't say a med that only helps ~33% of them time was a great result, but there's definitely a place for them as they help millions of people. Kind of like how anti-psychotics can be really damaging and have permanent, disabling affects for some people, but also allow millions to live normal lives.

Personally, I would 100% be dead without Sertraline/Zoloft.

Yes, true. I’m glad SSRIs worked for you. there’s probably always a place for strong medications like this. my problem isn’t really with the development of SSRIs or there use at a certain point of time, I just think that given their potentially serious side-effects it’s time we moved on from using them as a first line treatment. same with antipsychotics targeting the D2 receptors. given the rapidly advancing knowledge in the neuroscience field, there are plenty of new potential targets, yet pharmaceutical companies just focus on making new analogues of old drugs with practically the same mechanism of action. as I’ve mentioned on many threads including this one, the reward system plays a major role in depression. there are quite a few studies about the role of the nucleus accumbens in depression, so why is it that we are focusing so much on serotonin and so little on dopamine and glutamate.

 

[Skorpio]

^do you have a dumbed-down synopsis of that link lol?

Okay, first off, this is not really my field, so I'm going to miss a lot of nuance.

They show that there are regions in the cortex (which handles sensory procdssing) which regulate differentiating between images (and generally other stimuli) that are imagined or actually perceived (as they are only differentiated by their signal strength, with perceived signals being stronger).

They do this by putting mice in virtual reality setups where the simulation reacts to the mice so that there is feedback to their actions. They then put lapses or distortions on these to cause the mice to react to what they thought was occurring next.

The whole time these mice had different populations of neurons which would light up when they were active. These nice had cameras in their brains (literally referred to as the crystal skull at times in the paper due to its lens), and their brains were imaged when they were forced to make predictions due to the disruptions. They find that antipsychotics change patterns of neural firing during these lapsed events.

They go on to focus on subregions of the cortex which cause this effect, and then further to measure communications between regions in different layers of the cortex. They then give other antipsychotics and amphetamine to the mice to show that these effects generalize to antipsychotics, but not to dissimilar drugs like amphetamines.

The discussion provides a ton of detail and context, including caveats due to limitations of their study, but frankly it is quite long and goes into detail beyond my ability to really understand, let alone distill.

 

[Neuroprotection]

Something I’ve been thinking of for a long time, is the idea of adding a Brain specific tryptophan hydroxylase inhibitor (inhibits serotonin synthesis) to a non-selective MAOI like phenelzine or tranylcypromine. this is because those who benefit most from MAOI antidepressants are those who exhibit apathy, anhedonia and chronic lethargy. apparently, the ability of non-selected MAOIs to strongly boost norepinephrine and dopamine levels is what benefits these people most, whereas side-effects like sexual dysfunction which is less frequent than that of SSRIs still come from excessive serotonin. interestingly, I found a few small Study abstracts claiming that excessive serotonin synthesis is involved in some psychiatric disorders and that pharmacological inhibition of an enzyme called tryptophan hydroxylase2(TPH2) could be useful in these conditions. my rationale for adding a TPH2 inhibitor to a non-selective MAOI is that it would preferentially allow the increase of synaptic norepinephrine and dopamine levels as these molecules will be protected from degradation whilst additional new norepinephrine and dopamine molecules can be synthesised from incoming amino acids. meanwhile, whilst the non-selective MAOI would protect existing serotonin molecules, the TPH2 inhibitor can block synthesis of new serotonin thus maintaining serotonin at natural levels. this is important because serotonin accumulation during MAOI treatment has been shown to strongly dampen/limit dopaminergic activity.

 

[Neuroprotection]

SSRI-Induced Indifference

In the existing literature, selective serotonin reuptake inhibitor exposure has been occasionally associated with both behavioral apathy and emotional blunting. While frequently described as separate entities, these two syndromes are mutually characterized ...

www.ncbi.nlm.nih.gov

Scientists explain emotional ‘blunting’ caused by common antidepressants

Scientists have worked out why common anti-depressants cause around a half of users to feel emotionally ‘blunted’. In a study published today, they show that

www.cam.ac.uk

Selective serotonin reuptake inhibitors-associated apathy syndrome: A cross sectional study

Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with loss of motivation, anergy, and lack of curiosity often referred collectively as apathy. However, this association has not been systematically assessed ...

www.ncbi.nlm.nih.gov

SSRI destroyed my quality of life - Rare Disease Day 2023

My name is Alex, I am 30 years old and have simply been living in torture and agony since taking Escitaloptam over a year ago… Continue reading SSRI destroyed my quality of life

www.rarediseaseday.org

 

[Neuroborean]

I've heard good things about this plant.. Albizzia Julibrissin, working wonderfully as an antidepresant, but it needs to be extracted into a powerful extract, the flowers/bark are not enough.
More well known stuff, kanna, low dose yohimbe is super antidepressant but perhaps a lil bit anxyogenic...
also calamus root and peganum harmala are good natural, antidepressants. None of this are bad for sex/libido.

 

[Skorpio]

Something I’ve been thinking of for a long time, is the idea of adding a Brain specific tryptophan hydroxylase inhibitor (inhibits serotonin synthesis) to a non-selective MAOI like phenelzine or tranylcypromine. this is because those who benefit most from MAOI antidepressants are those who exhibit apathy, anhedonia and chronic lethargy. apparently, the ability of non-selected MAOIs to strongly boost norepinephrine and dopamine levels is what benefits these people most, whereas side-effects like sexual dysfunction which is less frequent than that of SSRIs still come from excessive serotonin. interestingly, I found a few small Study abstracts claiming that excessive serotonin synthesis is involved in some psychiatric disorders and that pharmacological inhibition of an enzyme called tryptophan hydroxylase2(TPH2) could be useful in these conditions. my rationale for adding a TPH2 inhibitor to a non-selective MAOI is that it would preferentially allow the increase of synaptic norepinephrine and dopamine levels as these molecules will be protected from degradation whilst additional new norepinephrine and dopamine molecules can be synthesised from incoming amino acids. meanwhile, whilst the non-selective MAOI would protect existing serotonin molecules, the TPH2 inhibitor can block synthesis of new serotonin thus maintaining serotonin at natural levels. this is important because serotonin accumulation during MAOI treatment has been shown to strongly dampen/limit dopaminergic activity.

What about just using selective MAO-B inhibitors? It seems like that should spare you the need for polypharmacy.

 

[Neuroprotection]

What about just using selective MAO-B inhibitors? It seems like that should spare you the need for polypharmacy.

Oh yes, in my case, that’s exactly what I’m planning to do. I want to try daily sublingual selegiline to tackle my chronic fatigue and extreme procrastination. nevertheless, selective MAOB inhibitors don’t raise dopamine as much as selective MAOa or non-selective inhibitors. furthermore, they don’t affect norepinephrine. this is because, MAOB apparently has quite a low affinity for dopamine and is more involved in metabolising phenylethylamine. for people with severe depression, a stronger elevation in dopamine and norepinephrine using strong non-selective inhibitors is generally required. unfortunately, the inevitable buildup of serotonin can go onto suppress dopamine neuron activity and dopamine release. that’s why I came up with the idea of adding a serotonin synthesis inhibitor. as I said before, I only intend to use selegiline at relatively high, but MAOB selective doses as elevated phenylethylamine enhances reward activity and elevates mood. another interesting but less well known aspect of MAOB inhibition is that it can slightly diminish GABA synthesis in certain areas of the brain, medial prefrontal cortex if I remember correctly, leading to stress resilience, which is something I could really benefit from.